There was no difference between arms in the rate of mucositis, dysphagia, xerostomia, or fatigue

Author's Conclusions

The addition of cetuximab to RT improves LRC and OS in a statistically and clinically meaningful way compared to RT alone

Minimal additive toxicities are noted with the addition of cetuximab. In particular, there was no increase in the rates of mucositis or dysphagia

Further investigation of cetuximab is warranted in other epithelial malignancies were RT plays a central role in treatment

Clinical/Scientific Implications

Cetuximab is one of the emerging drugs that have shown significant benefit in this new era of targeted therapy in oncologic treatment. This study shows an impressive improvement in LRC and OS with the addition of cetuximab to RT over RT alone. The benefits seen with cetuximab are comparable to those seen with the addition of chemotherapy to RT in locally advanced HNC with the important distinction that while concurrent chemotherapy and RT have significantly increased acute toxicities, cetuximab resulted in very little additional acute toxicity. In addition, this benefit was seen despite the fact that a variety of radiation techniques were used. Subgroup analyses were not performed and these data will be presented at a later date. It will be important to see if the different radiation techniques had an impact on the results of this trial. It is clear that altered fractionation strategies (hyperfractionation or accelerated fractionation) improve the overall outcome and have become standard in locally advanced head and neck cancer. Further follow-up is needed to determine whether this survival benefit holds and whether late toxicities may emerge.

It is important to note that the experimental arm of the trial was compared to RT alone. While there is a subset of patients who are appropriately treated with RT alone, increasingly, combined modality therapy has been used in patients with locally advanced HNC. The role of chemotherapy in addition to cetuximab and RT remain unclear, and future studies will need to examine the interplay of RT, chemotherapy, and targeted therapies such as cetuximab. In the meantime, the addition of cetuximab to patients with locally advance HNC who are treated with RT alone should be considered a reasonable approach.